“…However, there is experimental evidence that STZ-induced type 1 diabetic rats have low levels of AA in the plasma, liver, kidney, and other tissues [23,34,35]. It is conceivable that the enhanced oxidative stress in diabetes consumes the circulating AA and that the resulting diminution in the AA concentration leads to further enhancement of the reactions mediated by free radicals.…”
Diabetes mellitus is known to exacerbate cerebral ischemic injury. In the present study, we investigated antiapoptotic and anti-inflammatory effects of oral supplementation of ascorbic acid (AA) on cerebral injury caused by middle cerebral artery occlusion and reperfusion (MCAO/Re) in rats with streptozotocin-induced diabetes. We also evaluated the effects of AA on expression of sodium-dependent vitamin C transporter 2 (SVCT2) and glucose transporter 1 (GLUT1) after MCAO/Re in the brain. The diabetic state markedly aggravated MCAO/Re-induced cerebral damage, as assessed by infarct volume and edema. Pretreatment with AA (100 mg/kg, p.o.) for two weeks significantly suppressed the exacerbation of damage in the brain of diabetic rats. AA also suppressed the production of superoxide radical, activation of caspase-3, and expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) in the ischemic penumbra. Immunohistochemical staining revealed that expression of SVCT2 was upregulated primarily in neurons and capillary endothelial cells after MCAO/Re in the nondiabetic cortex, accompanied by an increase in total AA (AA + dehydroascorbic acid) in the tissue, and that these responses were suppressed in the diabetic rats. AA supplementation to the diabetic rats restored these responses to the levels of the nondiabetic rats. Furthermore, AA markedly upregulated the basal expression of GLUT1 in endothelial cells of nondiabetic and diabetic cortex, which did not affect total AA levels in the cortex. These results suggest that daily intake of AA attenuates the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to anti-apoptotic and anti-inflammatory effects via the improvement of augmented oxidative stress in the brain. AA supplementation may protect endothelial function against the exacerbated ischemic oxidative injury in the diabetic state and improve AA transport through SVCT2 in the cortex.
“…However, there is experimental evidence that STZ-induced type 1 diabetic rats have low levels of AA in the plasma, liver, kidney, and other tissues [23,34,35]. It is conceivable that the enhanced oxidative stress in diabetes consumes the circulating AA and that the resulting diminution in the AA concentration leads to further enhancement of the reactions mediated by free radicals.…”
Diabetes mellitus is known to exacerbate cerebral ischemic injury. In the present study, we investigated antiapoptotic and anti-inflammatory effects of oral supplementation of ascorbic acid (AA) on cerebral injury caused by middle cerebral artery occlusion and reperfusion (MCAO/Re) in rats with streptozotocin-induced diabetes. We also evaluated the effects of AA on expression of sodium-dependent vitamin C transporter 2 (SVCT2) and glucose transporter 1 (GLUT1) after MCAO/Re in the brain. The diabetic state markedly aggravated MCAO/Re-induced cerebral damage, as assessed by infarct volume and edema. Pretreatment with AA (100 mg/kg, p.o.) for two weeks significantly suppressed the exacerbation of damage in the brain of diabetic rats. AA also suppressed the production of superoxide radical, activation of caspase-3, and expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) in the ischemic penumbra. Immunohistochemical staining revealed that expression of SVCT2 was upregulated primarily in neurons and capillary endothelial cells after MCAO/Re in the nondiabetic cortex, accompanied by an increase in total AA (AA + dehydroascorbic acid) in the tissue, and that these responses were suppressed in the diabetic rats. AA supplementation to the diabetic rats restored these responses to the levels of the nondiabetic rats. Furthermore, AA markedly upregulated the basal expression of GLUT1 in endothelial cells of nondiabetic and diabetic cortex, which did not affect total AA levels in the cortex. These results suggest that daily intake of AA attenuates the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to anti-apoptotic and anti-inflammatory effects via the improvement of augmented oxidative stress in the brain. AA supplementation may protect endothelial function against the exacerbated ischemic oxidative injury in the diabetic state and improve AA transport through SVCT2 in the cortex.
“…An earlier study suggested that impairing hepatic regeneration and biosynthesis of AA decreased AA levels in the plasma and tissues of streptozotocin (STZ)-induce diabetic rats (Kashiba et al 2002 ). Another study examining the direct relationship between AA and STZ-induced diabetes in rats suggested that AA supplementation is associated with decreased levels of hyperglycemia, hyperlipidemia, and hyperketonemia (Clarke et al 1996 ). Moreover, the administration of AA to diabetic rats attenuated an increased CYP2E1 expression and concomitant ROS production and restored histologically modified liver tissue (Fig.…”
Section: Main Textmentioning
confidence: 99%
“…1 ), confirming the protective effect of AA on the liver injury (Ahn et al 2006 ). However, although STZ-treated rats displayed increased expression and activity of hepatic CYP1A, 2B, 2E, and 4A proteins, AA supplementation selectively reduced CYP2E activity and expression (Clarke et al 1996 ). Fig.…”
Diabetes mellitus (DM) is a metabolic disease that affects all systems in the body, including the liver. Numerous studies have reported that chronic DM etiology and pathogenesis complications implicate oxidative stress, generating reactive oxygen species, such as superoxide anions and free radicals. In addition, pro-inflammatory reactions are also underlying functions closely related to oxidative stress that further exacerbate pathological DM states. The liver is especially susceptible to hyperglycemia-induced oxidative stress and the related inflammation. Thus, anti-oxidation and anti-inflammation therapies are promising strategies for treating liver damage. This review summarizes therapeutic treatments attenuating the generation of oxidative stress and pro-inflammation, which also cause DM-induced liver injury. Although the treatments have several impediments to be solved, these remedies may have clinically important implications under the absence of effective drugs for the damaged liver in DM patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
